IL197965A - Compounds containing di-fluoro, pharmaceuticals containing them and their use in the preparation of medicines - Google Patents
Compounds containing di-fluoro, pharmaceuticals containing them and their use in the preparation of medicinesInfo
- Publication number
- IL197965A IL197965A IL197965A IL19796509A IL197965A IL 197965 A IL197965 A IL 197965A IL 197965 A IL197965 A IL 197965A IL 19796509 A IL19796509 A IL 19796509A IL 197965 A IL197965 A IL 197965A
- Authority
- IL
- Israel
- Prior art keywords
- alkyl
- compound
- optionally substituted
- amino
- independently selected
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 155
- 239000003814 drug Substances 0.000 title claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 13
- 238000002360 preparation method Methods 0.000 title claims description 7
- -1 dialkylammo Chemical group 0.000 claims description 166
- 125000000217 alkyl group Chemical group 0.000 claims description 115
- 125000003118 aryl group Chemical group 0.000 claims description 101
- 125000001188 haloalkyl group Chemical group 0.000 claims description 74
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 62
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 239000001257 hydrogen Substances 0.000 claims description 60
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 54
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 49
- 125000001072 heteroaryl group Chemical group 0.000 claims description 48
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 47
- 125000005843 halogen group Chemical group 0.000 claims description 46
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 39
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 39
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 38
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
- 150000003839 salts Chemical class 0.000 claims description 35
- 201000010099 disease Diseases 0.000 claims description 33
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 32
- 125000002252 acyl group Chemical group 0.000 claims description 31
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 31
- 125000002723 alicyclic group Chemical group 0.000 claims description 28
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 28
- 230000028993 immune response Effects 0.000 claims description 28
- 229910052799 carbon Inorganic materials 0.000 claims description 26
- 125000001153 fluoro group Chemical group F* 0.000 claims description 24
- 241001465754 Metazoa Species 0.000 claims description 22
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 22
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 18
- 125000002947 alkylene group Chemical group 0.000 claims description 16
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 16
- 238000002560 therapeutic procedure Methods 0.000 claims description 16
- 108090000613 Cathepsin S Proteins 0.000 claims description 15
- 102100035654 Cathepsin S Human genes 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- 125000001624 naphthyl group Chemical group 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 11
- 230000001404 mediated effect Effects 0.000 claims description 11
- 125000003282 alkyl amino group Chemical group 0.000 claims description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 8
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 7
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims description 6
- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 5
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 5
- 230000009885 systemic effect Effects 0.000 claims description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 4
- 208000006673 asthma Diseases 0.000 claims description 4
- 125000004980 cyclopropylene group Chemical group 0.000 claims description 4
- 125000005113 hydroxyalkoxy group Chemical group 0.000 claims description 4
- 206010025135 lupus erythematosus Diseases 0.000 claims description 4
- 206010028417 myasthenia gravis Diseases 0.000 claims description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 3
- 208000023328 Basedow disease Diseases 0.000 claims description 3
- 208000015023 Graves' disease Diseases 0.000 claims description 3
- 201000011152 Pemphigus Diseases 0.000 claims description 3
- ALBYIUDWACNRRB-UHFFFAOYSA-N hexanamide Chemical compound CCCCCC(N)=O ALBYIUDWACNRRB-UHFFFAOYSA-N 0.000 claims description 3
- 201000006417 multiple sclerosis Diseases 0.000 claims description 3
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
- 201000001976 pemphigus vulgaris Diseases 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 208000002193 Pain Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims description 2
- 230000036407 pain Effects 0.000 claims description 2
- IPWFJLQDVFKJDU-UHFFFAOYSA-N pentanamide Chemical compound CCCCC(N)=O IPWFJLQDVFKJDU-UHFFFAOYSA-N 0.000 claims 3
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 claims 2
- 150000002431 hydrogen Chemical group 0.000 claims 1
- 239000000203 mixture Substances 0.000 description 50
- 238000000034 method Methods 0.000 description 46
- 125000000623 heterocyclic group Chemical group 0.000 description 34
- 150000003254 radicals Chemical class 0.000 description 31
- 238000003786 synthesis reaction Methods 0.000 description 30
- 230000015572 biosynthetic process Effects 0.000 description 29
- 239000000243 solution Substances 0.000 description 28
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 239000002253 acid Substances 0.000 description 22
- 238000003556 assay Methods 0.000 description 22
- 150000001721 carbon Chemical group 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
- 238000011282 treatment Methods 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 239000012131 assay buffer Substances 0.000 description 15
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 230000007170 pathology Effects 0.000 description 14
- 102000005927 Cysteine Proteases Human genes 0.000 description 13
- 108010005843 Cysteine Proteases Proteins 0.000 description 13
- 102000004190 Enzymes Human genes 0.000 description 13
- 108090000790 Enzymes Proteins 0.000 description 13
- 229940088598 enzyme Drugs 0.000 description 13
- 125000001544 thienyl group Chemical group 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 125000006239 protecting group Chemical group 0.000 description 12
- 210000004027 cell Anatomy 0.000 description 11
- 230000014509 gene expression Effects 0.000 description 11
- 230000007062 hydrolysis Effects 0.000 description 11
- 238000006460 hydrolysis reaction Methods 0.000 description 11
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 11
- 108090000623 proteins and genes Proteins 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 125000002541 furyl group Chemical group 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 125000003373 pyrazinyl group Chemical group 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 150000001204 N-oxides Chemical class 0.000 description 8
- 125000004103 aminoalkyl group Chemical group 0.000 description 8
- 125000004663 dialkyl amino group Chemical group 0.000 description 8
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 125000002883 imidazolyl group Chemical group 0.000 description 8
- 125000003386 piperidinyl group Chemical group 0.000 description 8
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 108010054218 Factor VIII Proteins 0.000 description 7
- 102000001690 Factor VIII Human genes 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 235000001014 amino acid Nutrition 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- 229960000301 factor viii Drugs 0.000 description 7
- 239000003960 organic solvent Substances 0.000 description 7
- 125000004076 pyridyl group Chemical group 0.000 description 7
- 230000002829 reductive effect Effects 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- 229940124597 therapeutic agent Drugs 0.000 description 7
- 125000000335 thiazolyl group Chemical group 0.000 description 7
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 239000004215 Carbon black (E152) Substances 0.000 description 6
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical class [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 230000002939 deleterious effect Effects 0.000 description 6
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- 239000003112 inhibitor Substances 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 238000004519 manufacturing process Methods 0.000 description 6
- 125000002757 morpholinyl group Chemical group 0.000 description 6
- 230000003472 neutralizing effect Effects 0.000 description 6
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- 102000004169 proteins and genes Human genes 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
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- 102000035195 Peptidases Human genes 0.000 description 5
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- 238000010790 dilution Methods 0.000 description 5
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- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 5
- 238000013178 mathematical model Methods 0.000 description 5
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 5
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- 125000004193 piperazinyl group Chemical group 0.000 description 5
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
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- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- 108010092408 Eosinophil Peroxidase Proteins 0.000 description 4
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
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- 125000002950 monocyclic group Chemical group 0.000 description 4
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 4
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 4
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- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 description 4
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- SMTMSFHFPIGSBB-INIZCTEOSA-N (2s)-4,4-difluoro-5-phenyl-2-(phenylmethoxycarbonylamino)pentanoic acid Chemical compound C([C@@H](C(=O)O)NC(=O)OCC=1C=CC=CC=1)C(F)(F)CC1=CC=CC=C1 SMTMSFHFPIGSBB-INIZCTEOSA-N 0.000 description 2
- PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/45—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings
- C07C255/46—Carboxylic acid nitriles having cyano groups bound to carbon atoms of rings other than six-membered aromatic rings to carbon atoms of non-condensed rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/275—Nitriles; Isonitriles
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
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- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
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- Orthopedic Medicine & Surgery (AREA)
- Epidemiology (AREA)
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- Rheumatology (AREA)
- Biomedical Technology (AREA)
- Pulmonology (AREA)
- Neurosurgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Immunology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US84958706P | 2006-10-04 | 2006-10-04 | |
| PCT/US2007/080320 WO2008042968A2 (en) | 2006-10-04 | 2007-10-03 | Di-fluoro containing compounds as cysteine protease inhibitors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL197965A0 IL197965A0 (en) | 2009-12-24 |
| IL197965A true IL197965A (en) | 2014-08-31 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL197965A IL197965A (en) | 2006-10-04 | 2009-04-05 | Compounds containing di-fluoro, pharmaceuticals containing them and their use in the preparation of medicines |
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| Country | Link |
|---|---|
| US (1) | US7781487B2 (ko) |
| EP (1) | EP2079683B1 (ko) |
| JP (1) | JP5351030B2 (ko) |
| KR (2) | KR101486763B1 (ko) |
| AU (1) | AU2007303200B2 (ko) |
| CA (1) | CA2664878A1 (ko) |
| DK (1) | DK2079683T3 (ko) |
| EA (1) | EA022130B1 (ko) |
| ES (1) | ES2535603T3 (ko) |
| IL (1) | IL197965A (ko) |
| MX (1) | MX2009003563A (ko) |
| NZ (1) | NZ576105A (ko) |
| PT (1) | PT2079683E (ko) |
| TW (1) | TWI483720B (ko) |
| WO (1) | WO2008042968A2 (ko) |
| ZA (1) | ZA200902477B (ko) |
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| US7893112B2 (en) | 2006-10-04 | 2011-02-22 | Virobay, Inc. | Di-fluoro containing compounds as cysteine protease inhibitors |
| WO2009123623A1 (en) * | 2008-04-01 | 2009-10-08 | Virobay, Inc. | Di-fluoro containing compounds as cysteine protease inhibitors |
| CN102264695B (zh) * | 2008-11-13 | 2014-11-05 | 维罗贝股份有限公司 | 作为半胱氨酸蛋白酶抑制剂的含卤代烷基化合物 |
| US8324417B2 (en) * | 2009-08-19 | 2012-12-04 | Virobay, Inc. | Process for the preparation of (S)-2-amino-5-cyclopropyl-4,4-difluoropentanoic acid and alkyl esters and acid salts thereof |
| WO2020201572A1 (en) | 2019-04-05 | 2020-10-08 | Université De Bretagne Occidentale | Protease-activated receptor-2 inhibitors for the treatment of sensory neuropathy induced by a marine neurotoxic poisoning |
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| JP3599287B2 (ja) | 1993-04-28 | 2004-12-08 | 三菱化学株式会社 | スルホンアミド誘導体 |
| PL202226B1 (pl) | 1997-11-05 | 2009-06-30 | Novartis Ag | Nitryl dipeptydowy, jego zastosowanie lecznicze i zawierająca go kompozycja farmaceutyczna |
| US6685572B2 (en) | 1998-07-22 | 2004-02-03 | Ntn Corporation | Power transmission mechanism |
| US6395897B1 (en) * | 1999-03-02 | 2002-05-28 | Boehringer Ingelheim Pharmaceuticals, Inc. | Nitrile compounds useful as reversible inhibitors of #9 cathepsin 5 |
| JP2002539192A (ja) | 1999-03-15 | 2002-11-19 | アクシス・ファーマシューティカルズ・インコーポレイテッド | プロテアーゼ阻害剤としての新規な化合物及び組成物 |
| AU779177B2 (en) * | 1999-03-15 | 2005-01-13 | Axys Pharmaceuticals, Inc. | Novel compounds and compositions as protease inhibitors |
| EP1218372B1 (en) | 1999-09-13 | 2003-07-02 | Boehringer Ingelheim Pharmaceuticals, Inc. | Novel heterocyclic compounds useful as reversible inhibitors of cysteine proteases |
| US6420364B1 (en) * | 1999-09-13 | 2002-07-16 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compound useful as reversible inhibitors of cysteine proteases |
| US6492362B1 (en) | 1999-09-16 | 2002-12-10 | Axys Pharmaceuticals, Inc. | Compounds and compositions as cathepsin S inhibitors |
| AU779855B2 (en) | 2000-01-06 | 2005-02-17 | Axys Pharmaceuticals, Inc. | Novel compounds and compositions as protease inhibitors |
| WO2001068645A2 (en) | 2000-03-15 | 2001-09-20 | Axys Pharmaceuticals, Inc. | N-cyanomethylcarboxamides and their use as protease inhibitors |
| AU2002254099B2 (en) | 2001-03-02 | 2006-07-06 | Axys Pharmaceuticals, Inc. | Cathepsin cysteine protease inhibitors |
| SE521652C2 (sv) | 2001-03-15 | 2003-11-25 | Canag Diagnostics Ab | En skivepitelcellcancerrelaterad fusionsgen och motsvarande fusionsprotein |
| NZ528944A (en) | 2001-06-01 | 2007-09-28 | Axys Pharm Inc | Chemical compounds and pharmaceutical compositions as cathepsin S inhibitors |
| CN1324008C (zh) | 2001-09-14 | 2007-07-04 | 安万特药物公司 | 作为组织蛋白酶抑制剂的新化合物和组合物 |
| EP1434769A2 (en) | 2001-10-02 | 2004-07-07 | Boehringer Ingelheim Pharmaceuticals Inc. | Compounds useful as reversible inhibitors of cysteine proteases |
| WO2003037892A1 (en) * | 2001-10-29 | 2003-05-08 | Boehringer Ingelheim Pharmaceuticals, Inc. | Compounds useful as reversible inhibitors of cysteine proteases |
| WO2003041649A2 (en) * | 2001-11-13 | 2003-05-22 | Merck Frosst Canada & Co. | Cyanoalkylamino derivatives as protease inhibitors |
| PT1482924E (pt) | 2002-03-05 | 2008-08-27 | Axys Pharm Inc | Inibidores de proteases da cisteína catepsina |
| JP2006506326A (ja) | 2002-05-14 | 2006-02-23 | アキシーズ ファーマシューティカルズ インク． | システインプロテアーゼ阻害剤 |
| US7101880B2 (en) * | 2002-06-24 | 2006-09-05 | Schering Aktiengesellschaft | Peptidic compounds as cysteine protease inhibitors |
| WO2004033445A1 (en) | 2002-10-08 | 2004-04-22 | Merck Frosst Canada & Co. | 4-amino-azepan-3-one compounds as cathepsin k inhibitors useful in the treatment of osteoporosis |
| US7326719B2 (en) | 2003-03-13 | 2008-02-05 | Boehringer Ingelheim Pharmaceuticals, Inc. | Cathepsin S inhibitors |
| CA2526694A1 (en) | 2003-06-04 | 2004-12-16 | John W. Patterson | Amidino compounds as cysteine protease inhibitors |
| EP1660436A4 (en) | 2003-08-27 | 2006-11-22 | Merck Frosst Canada Ltd | cathepsin inhibitors |
| JP2007505919A (ja) | 2003-09-18 | 2007-03-15 | アクシス・ファーマシューティカルズ・インコーポレイテッド | システイン・プロテアーゼ阻害剤としてのハロアルキル含有化合物 |
| SG146658A1 (en) | 2003-09-18 | 2008-10-30 | Schering Ag | Haloalkyl containing compounds as cysteine protease inhibitors |
| RU2346943C2 (ru) * | 2003-10-24 | 2009-02-20 | Авентис Фармасьютикалз Инк. | Новые соединения и композиции в качестве ингибиторов катепсина |
| JP2007513972A (ja) | 2003-12-11 | 2007-05-31 | アクシス・ファーマシューティカルズ・インコーポレイテッド | 低分子治療剤または生物製剤の投与によって引き起こされる免疫応答を治療するためのカテプシンｓインヒビターの使用 |
| CN100548986C (zh) * | 2003-12-12 | 2009-10-14 | 默克弗罗斯特加拿大有限公司 | 组织蛋白酶半胱氨酸蛋白酶抑制剂 |
| EP1697355A2 (en) | 2003-12-23 | 2006-09-06 | Axys Pharmaceuticals, Inc. | Amidino compounds as cysteine protease inhibitors |
| JP2007519744A (ja) | 2004-01-30 | 2007-07-19 | バイエル・シエーリング・ファーマ アクチエンゲゼルシャフト | システインプロテアーゼインヒビターとしてのシリナン化合物。 |
| CN101068783A (zh) | 2004-09-17 | 2007-11-07 | 拜耳先灵制药有限公司 | 用于制备半胱氨酸蛋白酶抑制剂的方法和中间体 |
| AR055283A1 (es) * | 2004-11-23 | 2007-08-15 | Merck Frosst Canada Ltd | Inhibidores de cisteinproteasa de catepsina |
| US7893112B2 (en) * | 2006-10-04 | 2011-02-22 | Virobay, Inc. | Di-fluoro containing compounds as cysteine protease inhibitors |
-
2007
- 2007-10-03 CA CA002664878A patent/CA2664878A1/en not_active Abandoned
- 2007-10-03 JP JP2009531585A patent/JP5351030B2/ja not_active Expired - Fee Related
- 2007-10-03 DK DK07853752.9T patent/DK2079683T3/en active
- 2007-10-03 KR KR1020097009231A patent/KR101486763B1/ko active IP Right Grant
- 2007-10-03 WO PCT/US2007/080320 patent/WO2008042968A2/en active Application Filing
- 2007-10-03 AU AU2007303200A patent/AU2007303200B2/en not_active Ceased
- 2007-10-03 ES ES07853752.9T patent/ES2535603T3/es active Active
- 2007-10-03 EP EP07853752.9A patent/EP2079683B1/en active Active
- 2007-10-03 PT PT78537529T patent/PT2079683E/pt unknown
- 2007-10-03 ZA ZA200902477A patent/ZA200902477B/xx unknown
- 2007-10-03 KR KR1020147015354A patent/KR101555931B1/ko active IP Right Grant
- 2007-10-03 MX MX2009003563A patent/MX2009003563A/es active IP Right Grant
- 2007-10-03 EA EA200900510A patent/EA022130B1/ru not_active IP Right Cessation
- 2007-10-03 US US11/866,836 patent/US7781487B2/en active Active
- 2007-10-03 NZ NZ576105A patent/NZ576105A/en not_active IP Right Cessation
-
2008
- 2008-04-02 TW TW097112047A patent/TWI483720B/zh not_active IP Right Cessation
-
2009
- 2009-04-05 IL IL197965A patent/IL197965A/en active IP Right Grant
Also Published As
| Publication number | Publication date |
|---|---|
| WO2008042968A3 (en) | 2008-05-22 |
| IL197965A0 (en) | 2009-12-24 |
| AU2007303200A1 (en) | 2008-04-10 |
| US20080214676A1 (en) | 2008-09-04 |
| KR101486763B1 (ko) | 2015-01-28 |
| WO2008042968A2 (en) | 2008-04-10 |
| NZ576105A (en) | 2012-01-12 |
| ZA200902477B (en) | 2010-08-25 |
| TW200942232A (en) | 2009-10-16 |
| JP5351030B2 (ja) | 2013-11-27 |
| CA2664878A1 (en) | 2008-04-10 |
| ES2535603T3 (es) | 2015-05-13 |
| DK2079683T3 (en) | 2015-04-27 |
| AU2007303200B2 (en) | 2011-10-06 |
| EP2079683B1 (en) | 2015-01-21 |
| KR20140112479A (ko) | 2014-09-23 |
| JP2010505872A (ja) | 2010-02-25 |
| US7781487B2 (en) | 2010-08-24 |
| PT2079683E (pt) | 2015-05-20 |
| EA022130B1 (ru) | 2015-11-30 |
| MX2009003563A (es) | 2009-04-15 |
| EA200900510A1 (ru) | 2009-08-28 |
| KR101555931B1 (ko) | 2015-09-30 |
| EP2079683A2 (en) | 2009-07-22 |
| KR20090085612A (ko) | 2009-08-07 |
| TWI483720B (zh) | 2015-05-11 |
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